Methods and apparatuses for detecting microscope slide coverslips

ABSTRACT

A system is capable of detecting substrates and can differentiate between zero, one, or multiple transparent or semi-transparent substrates in a stack. The system can include an optical sensor, an optically anti-reflective element, and a detector. The optical sensor outputs light towards the optically anti-reflective element. The light detector is positioned to detect light from the light source that is reflected by substrates, if any, positioned within a detection zone between the optically anti-reflective element and the detector.

TECHNICAL FIELD

This disclosure relates to methods and apparatuses for analyzingsubstrates. In particular, the disclosure relates to methods andapparatuses for detecting coverslips for microscope slides.

BACKGROUND

A wide variety of techniques have been developed to prepare and analyzebiological samples for analysis. Biological samples, e.g., tissuesections or cells, can be mounted on microscope slides for diagnosticpurposes. The biological samples are often treated with one or moresubstances (e.g., dyes, reagents, etc.) to add color and contrast tootherwise transparent or invisible cells or cell components. The treatedbiological samples are often covered with coverslips to avoidcontamination of the biological samples and to permit long-termarchiving of the slides.

Automated coverslippers can be used to automatically place glasscoverslips on specimen-bearing microscope sides. For example, automatedcoverslippers often pick up a coverslip from a stack of coverslips andplace the coverslip onto a specimen-bearing slide. Unfortunately,automated coverslippers can pick up more than one coverslip becausecoverslips frequently stick together due to static forces, vander waalforces, or moisture between adjacent coverslips. This may result in twoor more coverslips being mounted on a slide. It may be difficult toremove the excess coverslip(s) from the slide. If the automatedcoverslipper attempts to transport stuck-together slides, coverslips maydrop resulting in loose coverslips in automated processing equipment.The loose coverslips can result in damage and/or malfunction of theautomated processing equipment and may result in “downtime” formaintenance. Unfortunately, automated coverslippers are not capable ofaccurately counting coverslips during handling.

Overview of Technology

At least some embodiments of the technology are directed to a system fordetecting substrates. The system is capable of differentiating betweenzero, one, or multiple substrates in a stack. The system can detectsubstrates in the form of, for example, coverslips (e.g., coverslips formicroscope slides), screens (e.g., transparent screens for computingdevices, smartphones, tablets, or the like), protective sheets, or otheritems through which electromagnetic radiation is capable of traveling.The substrates can be transparent or semi-transparent.

In some embodiments, a system for detecting substrates includes anoptically anti-reflective element and an optical sensor. The opticalsensor includes a light source and a light detector. The light source ispositioned to output light towards the optically anti-reflectiveelement. The light detector is positioned to detect the light reflectedby one or more substrates located between the light detector and theoptically anti-reflective element. Information about the substrates canbe determined based on the reflected light. The information can include,for example, the presence of substrates, the number of substrates,optical properties of the substrates, or the like. For example, thereflected light can be used to count the number of substrates in a stackof substrates.

The optically anti-reflective element, in some embodiments, can absorbincident or impinging light to manage noise (e.g., optical noise). Thenoise can be, for example, light reflected from surfaces adjacent to thesubstrates. In some embodiments, the optically anti-reflective elementcan be positioned to limit, reduce, or substantially eliminate noisecaused by such reflected light. The reflected light (i.e., the signalfrom the substrates) received by the light detector can thus be used toaccurately detect the substrates.

In some embodiments, a substrate analyzer can include an optical sensorand an optical element. A holder mechanism can carry one or moresubstrates to a detection zone between the sensor and optical element.The substrate analyzer can evaluate the detection zone to count thenumber of substrates, if any, within the detection zone. The opticalsensor can be carried by, or part of, the holder mechanism such that theoptical sensor is properly positioned with respect to the substrate. Insome embodiments, the optical sensor and optical element are stationary.The holder mechanism can carry substrates into the detection zone. Inother embodiments, the optical sensor can be stationary and the opticalelement is part of the holder mechanism.

In some embodiments, a detector comprises an optical element and anoptical sensor. In one embodiment, the optical element is anoise-reducing element that inhibits, limits, or substantially preventsthe reflection of light that has traveled through a stack of substrates.The noise-reducing element can include, without limitation, one or moreoptically anti-reflective elements with low-remission surfaces,light-absorbing characteristics, or the like.

In some embodiments, a slide processing apparatus includes a processingstation configured to process a specimen on a microscope slide and acoverslipper. The coverslipper receives and applies coverslips tomicroscope slides processed by the processing station. The coverslippercan include one or more coverslip detectors used to detect coverslips. Acoverslip detector, in some embodiments, includes an opticallyanti-reflective element and an optical sensor. The optical sensor ispositioned to deliver light along a path towards the anti-reflectiveelement and to detect light reflected by any coverslips positioned alongthe path. In some embodiments, the coverslip detectors can include anarray of light sensors and detectors to simultaneously analyze multiplecoverslips.

In one embodiment, a detection method comprises delivering light towardsa coverslip such that a portion of the light is reflected by thecoverslip and a portion of the light travels through the coverslip andstrikes an optically anti-reflective element. The light reflected by thecoverslip can be detected to, for example, determine a presence or anumber of coverslips. In one embodiment, the coverslip is held againstthe optically anti-reflective element while detecting the reflectedlight. For example, the coverslip can cover the opticallyanti-reflective element.

In some embodiments, a method of detecting substrates includes carryingat least one substrate to a detection zone using a holder mechanism. Thedetection zone can be located between a light detector and an opticallyanti-reflective element. Light is delivered towards the opticallyanti-reflective element such that a portion of the light is reflected bythe substrate and a portion of the light, which travels through thesubstrate, strikes the optically anti-reflective element. The lightreflected by the substrate can be detected, and a number of substratesat the detection zone can be determined based on the detected light.

A delivery location of the substrates can be determined based, at leastin part, on the presence or number of substrates. A controller, in someembodiments, can determine the delivery location based on the number ofdetected substrates. In some embodiments, the controller can command theholder mechanism to move the substrates to a first location if onesubstrate is detected and a second location a plurality of substratesare detected.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments are described with referenceto the following drawings. The same reference numerals refer to likeparts or acts throughout the various views, unless otherwise specified.

FIG. 1 is a front view of a coverslip detector in accordance with oneembodiment.

FIG. 2 is a side view of the coverslip detector of FIG. 1.

FIG. 3 is a detailed view of the coverslip detector of FIG. 1.

FIG. 3A is a detailed view of an anti-reflective coating and coverslipcross-section.

FIG. 3B is a detailed view of an optical element along line-line 3B-3Bof FIG. 3.

FIG. 4 is a detailed view of a coverslip detector holding twocoverslips.

FIG. 5 is a front view of an automated coverslipper ready to pick up acoverslip in accordance with one embodiment.

FIG. 6 is a front view of the coverslipper of FIG. 5 holding a coverslipproximate to an optical sensor in accordance with one embodiment.

FIG. 7 is a front view of the coverslipper of FIG. 5 placing a coverslipon a specimen-bearing slide in accordance with one embodiment.

FIG. 8 is a front view of a coverslipper in accordance with anotherembodiment.

FIG. 9 is a front view of a coverslip detector in accordance withanother embodiment.

FIG. 10 is a cross-sectional view of the coverslip detector taken alongline 10-10 of FIG. 9.

FIG. 11 is a front view of a coverslip detector in accordance withanother embodiment.

FIG. 12 is an isometric view of an automated slide processing apparatusin accordance with one embodiment.

FIG. 13 is a side view of the automated slide processing apparatus ofFIG. 12.

FIG. 14 is a cross-sectional view of the automated slide processingapparatus taken along line 14-14 of FIG. 13.

DETAILED DESCRIPTION OF TECHNOLOGY

FIGS. 1 and 2 are front and side views of a coverslip detector 100 inaccordance with one embodiment. The coverslip detector 100 can include acoverslip transport apparatus 110 (“transport apparatus 110”) forcarrying microscope slide coverslips and an optical sensor 120 fordetecting coverslips. The transport apparatus 110 is shown carrying asingle microscope slide coverslip 130. A detection enhancing element inthe form of an optically anti-reflective element 160 (“anti-reflectiveelement 160”) can be positioned behind the surface of the coverslip 130opposite the optical sensor 120. The anti-reflective element 160 canenhance performance of the optical sensor 120 to accurately detect apresence and/or number of coverslips held by the transport apparatus110. The enhanced performance can include, without limitation,increasing the detection range of the sensor 120, reducing or limitingnoise to increase a signal-to-noise ratio, managing scattering of light,or combinations thereof. After the optical sensor 120 determines thatthe transport apparatus 110 is carrying the single coverslip 130, thecoverslip 130 can be placed on a specimen-bearing microscope slide. Ifthe optical sensor 120 detects multiple coverslips, the transportapparatus 110 can transport the coverslips to a coverslip collectionstation or another desired location. If the optical sensor 120determines that the transport apparatus 110 is unloaded, the transportapparatus 110 can obtain a coverslip.

The optical sensor 120 can be a photoelectric proximity sensorconfigured to output light towards the anti-reflective element 160 anddetect light reflected by the coverslip 130. In some embodiments, thedetection of light can include, for example, one or more of determiningthe presence of light, measuring light intensity, comparing measuredlight intensity to a reference light intensity, or the like. Theanti-reflective element 160 can minimize, limit, or substantiallyeliminate reflection of light that has traveled through the coverslip130 because such reflected light may result in noise. The percentage ofincident light from the sensor 120 absorbed or otherwise captured by theanti-reflective element 160 can be increased or decreased to increase ordecrease the signal (e.g., light intensity associated with lightreflected by the coverslips) to noise ratio.

Referring to FIG. 1, the transport apparatus 110 can include a transportmechanism 140 and a coverslip holder mechanism 144 (“holder mechanism144”). The transport mechanism 140 can move the holder mechanism 144 toposition at least a portion of the coverslip 130 within a coverslipdetection zone 163. The transport mechanism 140 can include, withoutlimitation, one or more robotic arms, conveyors, motors (e.g., stoppermotors, drive motors, etc.), rail assemblies (e.g., carriage and linearrail assemblies), controllers, combinations thereof, or the like. Thecomponents and configuration of the transport mechanism 140 can beselected based on the desired movement of the holder mechanism 144.

The holder mechanism 144 can include a main body 150, a fluid line 152,and a pickup head 154 (“head 154”). The head 154 is positioned in themain body 150 and is shown in dashed line. The main body 150 can have aone-piece construction or a multi-piece construction and can fluidicallycouple the fluid line 152 to the head 154. The line 152 can include,without limitation, one or more conduits (e.g., hoses), valves, or otherfluid components for establishing a fluidic connection between the mainbody 150 and a pressurization device 170. The head 154 can be a suctionhead (e.g., a suction cup) capable of maintaining a vacuum with thecoverslip 130. The pressurization device 170 can draw a vacuum such thata sufficient vacuum is maintained to securely hold the coverslip 130. Torelease the coverslip 130, the vacuum can be reduced or eliminated. Thepressurization device 170 can include, without limitation, one or morevacuum devices, pumps, or the like.

A controller 180 can be in communication with the sensor 120 and candetermine the number of coverslips carried by the holder mechanism 144.In some embodiments, the controller 180 can correlate the detected lightto the absence, presence, and/or number of coverslips based on signalsfrom the sensor 120. The controller 180 can thus determine the number ofcoverslips based on the total amount of detected light because the totalamount of received light can be directly related to the number ofcoverslips. The controller 180 can also be integrated into the sensor120.

FIG. 3 is a detailed view of the coverslip 130 held flat against theholder mechanism 144. A back surface 181 of the coverslip 130 can beheld in contact with a contact surface 183 of the holder mechanism 144to minimize scattering of light transmitted through the coverslip 130and/or to prevent unwanted movement of the coverslip 130. In otherembodiments, the back surface 181 of the coverslip 130 can be spacedapart from the contact surface 183 to prevent or inhibit sticking of thecoverslip 130 to the holder mechanism 144.

The sensor 120 can be a proximity sensor. Proximity sensors include,without limitation, photoelectric proximity sensors (e.g.,retro-reflective photoelectric proximity sensors, diffuse-reflectivephotoelectric proximity sensors, etc.) or other sensors capable ofdetecting coverslips based on, for example, optical analysis (e.g.,analysis of reflected light, scattered light, etc.). Advantageously, adistance (i.e., a detector distance) at which the sensor 120 detects asignal above a target threshold can increase for additional coverslips.In some embodiments, the detector distance D can increase, for example,about 60 times the thickness 0.18 mm (0.007 inch) of each additionalcoverslip. Thus, the detection distance D for two coverslips can be 10.8mm greater than the detection distance D for a single coverslip. In oneembodiment, the sensor 120 is a photoelectric proximity sensor from SickAG, Waldkirch, DE or similar sensor capable of accurately detecting thepresence of the coverslip 130. The sensor 120 can include a positionermechanism 191 (shown in dashed line in FIG. 1) to move the opticalsensor 120 towards or away from the coverslip 130 to adjust the distanceD, thereby providing detection flexibility.

FIGS. 3 and 3A are detailed views of the coverslip detector 100 andcoverslip 130. Referring to FIG. 3, the optical sensor 120 can include alight source 174 and a light detector 178. The light source 174 can emitlight 200 (e.g., a beam of light) that travels generally along alight/optical path 204 towards the coverslip 130. A front surface 211 ofthe coverslip 130 can reflect a portion of the incident light 200. Thereflected light (represented by arrow 210) can be received by the lightdetector 178, and transmitted light (represented by arrow 214 in FIG.3A) can be absorbed by the anti-reflective element 160. The percentageof transmitted light 214 absorbed by the anti-reflective element 160 canbe selected to keep the signal-to-noise ratio at or above a desiredlevel.

In some embodiments, the anti-reflective element 160 may reflect aportion of the light 214. This reflected light (represented by arrow 213in FIG. 3A) can travel through the coverslip 130 towards the detector178. There may be transmission losses due to transmission through thecoverslip 130. The signal (i.e., the light) detected by the detector 178can correspond to the sum of the light 210, 213′.

Referring again to FIG. 3, the light source 174 can include, withoutlimitation, one or more light sources or light generators capable ofemitting electromagnetic radiation, including, but not limited to,visible light waves, non-visible light waves, infrared light waves, orcombinations thereof. The light sources can be, for example, lightemitting diodes (e.g., edge emitting LEDs, surface emitting LEDs, superluminescent LEDs), laser diodes, or other suitable light-emittingsources. The light detector 178 can detect radiation wavelength(s) orwaveband(s) that corresponds with, or at least overlap with, thewavelength(s) or waveband(s) outputted by the light source 174. Theoptical sensor 120 can also include, without limitation, one or moreoptic elements (e.g., lenses, filters, etc.), amplifiers, powersupplies, circuitry, memory, controllers, or the like.

The optically anti-reflective element 160 can inhibit, minimize, orsubstantially prevent the reflection of incident light. In someembodiments, the optically anti-reflective element 160 has reflectivity(or reflectance) of about 0.5 or less for the light outputted by thelight source 174. In some embodiments, the light detector 178 includes aphotoelectric receiver configured to detect light at one or morewavelengths, and the optically anti-reflective element 160 can have areflectivity (e.g., a reflectivity equal to or less than about 0.5,0.25, or 0.1) for the light at the one or more wavelengths. In oneembodiment, the optically anti-reflective element 160 has a reflectivity(or reflectance) of about 0.25 or less for the light outputted by thelight source 174 or the light detectable by the light detector 178. Inone embodiment, the optically anti-reflective element 160 has areflectivity (or reflectance) of about 0.1 or less for the lightoutputted by the light source 174 or the light detectable by the lightdetector 178. The optical characteristics of the anti-reflective element160 can be selected based on the light emitted by the light source 174and capabilities of the light detector 178.

In some embodiments, the anti-reflective element 160 is alight-absorbing, low-remission surface. For example, thelight-absorbing, low-remission surface can be an anodized surface. Thepercentage of incident light reflected from the anodized surface (e.g.,anodized aluminum) can be less than 50% of the incident light strikingthe anti-reflective element 160. In one embodiment, the low-remissionsurface can be a coating, such as a light absorbing coating. In oneembodiment, the anti-reflective element 160 is a black coating, blackfilm, black piece of plastic (e.g., a piece of plastic with a blacksurface), or black paper. In one embodiment, the anti-reflective element160 includes a light absorbing element and an anti-reflection coating onthe light absorbing element. The optical characteristics andconfiguration of the optically anti-reflective element 160 can beselected to achieve the desired detected signal. Such opticalcharacteristics can include a low reflectivity, low reflection (e.g.,low specular reflection, low diffuse reflection, etc.), or the like. Thepercentage of incident light that is absorbed by the element 160 can beincreased or decreased to increase or decrease a ratio of the amount ofreflected light 210 to the amount of light 213.

FIG. 3B is a detailed view of the anti-reflective element 160 alongline-line 3B-3B of FIG. 3. A target or exposure area 277 (illustrated indashed line) is the area that can be illuminated by the sensor 120. Theentire area 277 can be located along an exposed surface 279 of theanti-reflective element 160 and can be spaced apart from edges 281 a,281 b, 281 c, 281 d. If the coverslip 130 scatters the transmittedlight, a region 291 of the anti-reflective element 160 surrounding thearea 277 can absorb the scattered light. In some embodiments, the targetarea 277 can be positioned at a central region of the anti-reflectiveelement 160.

FIG. 4 is a detailed view of the coverslip detector 100 holding twocoverslips 130 a, 130 b (collectively “coverslips 130”) along a lightpath 214. Light (represented by arrow 200) from the optical sensor 120can be reflected by each of the coverslips 130. The optical sensor 120can detect light (represented by arrow 270) reflected by the coverslip130 a and light (represented by arrow 272) reflected by the coverslip130 b, as well as light (represented by arrow 274), if any, reflected bythe optically anti-reflective element 160. The optical sensor 120 candetect the received light, which comprises the light 270, 272, 274, andoutput a signal corresponding to the detected light. Because the returnsignal (i.e., the received light) can increase significantly for eachadditional coverslip, the return signal can be strongly correlated tothe number of coverslips 130 and weakly correlated to the thicknesst_(s) of the stack.

FIG. 5 is a front view of a coverslipper 300 ready to pick up acoverslip 130 in accordance with one embodiment. FIG. 6 is a front viewof the coverslipper 300 ready to detect the number of coverslips carriedby the holder mechanism 144. FIG. 7 is a front view of the coverslipper300 placing the coverslip 130 on a specimen-bearing slide 332. Referringto FIG. 5, the coverslipper 300 can include a coverslip loading orpickup station 310 (“loading station 310”), a detection station 320, anda mounting station 322. The loading station 310 can include a carrier330 (e.g., a cassette, a cartridge, a magazine, etc.) holding coverslips130 stacked in a substantially vertical arrangement but can includeother types of carriers (e.g., trays that carry coverslips in ahorizontal arrangement).

The coverslips 130 can be generally circular shaped, rectangular shaped,square shaped, or any other suitable shape. In some embodiments, thecoverslips are circular with diameters of 18 mm, 22 mm, or 25 mm. Squarecoverslips 130 can have sides with lengths of about 18 mm, 22 mm, or 25mm. Rectangular coverslips 130 can have sides with lengths from about 11mm×22 mm to about 48 mm×60 mm. The dimensions, shapes, and properties ofthe coverslips can be selected based on, for example, the size of themicroscope slides. The coverslips 130 can be made, in whole or in part,of transparent plastic, glass, or other transparent or semi-transparentmaterials. In some embodiments, bottom surfaces of coverslips (e.g.,glass plate coverslips) are coated with an adhesive, such as anactivatable adhesive. The activatable adhesives can be, for example, dryactivatable toluene, xylene, or the like.

FIG. 5 shows the holder mechanism 144 positioned at a loading or pickupposition 307. The pickup head 154 is at a lowered or deployed positionto contact or be close to the upper surface 181 of the uppermostcoverslip 130 such that a vacuum can be drawn to hold the upper surface181 against the head 154. After the holder mechanism 144 holds thecoverslip 130, the transport mechanism 140 can lift the coverslip 130from the stack 301. Additionally or alternatively, a reciprocallymovable plunger 312 can move through a bottom portion 313 of the carrier330 to push the uppermost coverslip 130 into contact with the head 154.The plunger 312 can also be lowered to separate the stack 301 from thecoverslip 130 retained by the pickup head 154.

The transport mechanism 140 can move the holder mechanism 144 from theloading station 310 to the detection station 320. FIG. 6 shows theholder mechanism 144 at a detection position such that the coverslip 130is located at the detection zone 163. The front surface 211 of thecoverslip 130 can be generally perpendicular to the light path 214 suchthat light reflected by the surface 211 travels back towards the sensor120. For example, the angle of incidence can be equal to or less thanabout 5 degrees. Other angles of incidence are also possible.

After determining the holder mechanism 144 is holding only onecoverslip, the holder mechanism 144 can carry the coverslip 130 to themounting station 322. If the detection station 320 determines that thetransport apparatus 110 is carrying multiple coverslips (e.g., a stackof coverslips stuck together), the transport apparatus 110 can deliverthe coverslips to a rejected coverslip collection station. The rejectedcoverslip collection station can include one or more receptacles,cassettes, magazines, and can be periodically emptied or discarded.

FIG. 7 shows the coverslip 130 covering a specimen 340. The mountingstation 322 can include, without limitation, a platform 336 configuredto support the slide 332. The specimen 340 can be a biological specimenthat includes one or more biological samples, which can be a tissuesample removed from a subject. The tissue sample can be a collection ofcells, such as interconnected cells that perform a similar functionwithin an organism. A biological sample can also be any solid or fluidsample obtained from, excreted by, or secreted by any living organism,including, without limitation, single-celled organisms, such asbacteria, yeast, protozoans, and amebas, multicellular organisms (e.g.,plants or animals, including samples from a healthy or apparentlyhealthy human subject or a human patient affected by a condition ordisease to be diagnosed or investigated, such as cancer). In someembodiments, a biological sample includes, without limitation, a sectionof tissue, an organ, a tumor section, a smear, a frozen section, acytology prep, or cell lines. An incisional biopsy, a core biopsy, anexcisional biopsy, a needle aspiration biopsy, a core needle biopsy, astereotactic biopsy, an open biopsy, or a surgical biopsy can be used toobtain the sample.

The slide 332 can be a 1 inch×3 inch microscope slide, a 25 mm×75 mmmicroscope slide, or another type of flat or substantially flatsubstrate. “Substantially flat substrate” refers, without limitation, toany object having at least one substantially flat surface, but moretypically to any object having two substantially flat surfaces onopposite sides of the object, and even more typically to any objecthaving opposed substantially flat surfaces, which opposed surfaces aregenerally equal in size but larger than any other surfaces on theobject. In some embodiments, the substantially flat substrate cancomprise any suitable material, including plastics, rubber, ceramics,glass, silicon, semiconductor materials, metals, combinations thereof,or the like. Non-limiting examples of substantially flat substratesinclude SELDI and MALDI chips, silicon wafers, or other generally planarobjects with at least one substantially flat surface.

Referring to FIGS. 5-7, the coverslipper 300 can be an automatedcoverslipper. Coverslips and/or specimen-bearing slides can be manuallyloaded into the coverslipper 300, which can sequentially cover eachspecimen-bearing microscope slide with a single coverslip. Thecoverslipped microscope slides can be removed from the coverslipper 300for analysis and/or storage.

FIG. 8 shows a portable coverslipper 400 that can be readily carried bya person. In a laboratory setting, the coverslipper 400 can be manuallytransported between workstations and can include a protective housing402 for inhibiting, limiting, or substantially preventing contaminantsfrom entering an internal chamber 410. The protective housing 402 caninclude, without limitation, a cover or a door that can be opened toaccess internal components, including, without limitation, transportapparatus 412 (e.g., conveyors, actuators, etc.), robotic components(e.g., robotic arms), slide holding stations, or the like. For example,the cover can be opened to manually place a coverslip carrier 330(illustrated loaded with a stack of coverslips) into the loading station310.

FIG. 9 is a front view of a coverslip detector 404 that is generallysimilar to the coverslip detector 100 discussed in connection with FIGS.1-7, except as detailed below. The coverslip detector 404 can include acoverslip holder mechanism 422 and a backing element 424. The coverslipholder mechanism 422 can include a main body 428, a sensor 430, andpickup heads 432 a, 432 b (collectively “pickup heads 432”). A vacuumcan be drawn between the heads 432 and a coverslip 440 via a line 442.The backing element 424 can include an optical element 446 (e.g., anoise reducing element, an optically anti-reflective element, etc.) toenhance performance of the sensor 430. A detection zone 447 is definedbetween the coverslip holder mechanism 422 and the optical element 446.In some embodiments, the sensor 430 can be mounted on a backside of themain body 428. In other embodiments, the sensor 430 can be embedded inthe main body 428 or located at another position.

FIG. 10 is a cross-sectional view of the coverslip detector 404 alongline 10-10 of FIG. 9. The sensor 430 includes a light source 450 thatcan produce light (represented by arrow 454) that travels through anopening 460 (e.g., a through hole, an aperture, etc.) in the main body428. For example, the diameter of the opening 460 can be decreased orincreased to decrease or increase scattering of light. A portion of thelight 454 can be reflected by a front surface 439 of the coverslip 440and detected (e.g., identified, measured, analyzed, etc.) by a lightdetector 452. The optical element 446 can be positioned on the backside441 of the coverslip 440 to inhibit, limit, or to substantiallyeliminate noise attributable of reflection by the backing element 424.In some embodiments, the coverslip 440 lays generally flat on thebacking element 424 such that the backside surface 443 contacts an uppersurface 447 of the optical element 446.

FIG. 11 is a front view of a stationary coverslip detector 470 inaccordance with another embodiment. The coverslip detector 470 can begenerally similar to the detectors discussed in connection with FIGS.1-10, except as detailed below. The coverslip detector 470 can include acoverslip holder mechanism 472 (“holder mechanism 472”) and a backingelement 474. The holder mechanism 472 can mechanically hold and releasecoverslips using arms 476 a, 476 b (collectively “arms 476”). In otherembodiments the mechanical holder mechanism 472 can include one or morepins, lifters, pinchers, clamps, or the like.

The holder mechanism 472 can transport the coverslip 440 from a loadingstation to a detection zone 481. Advantageously, the stationarycoverslip detector 470 can analyze coverslips carried by different typesof holder mechanisms. The coverslip detector 470 can include a sensor483 mounted to a backing element 484, which includes an optical element486. After a portion 487 of the coverslip 480 is positioned within thedetection zone 481, the sensor 483 can determine the number ofcoverslips.

FIG. 12 is an isometric view of an automated slide processing apparatus500 (“apparatus 500”) that includes processing stations 502 a, 502 b,502 c, 502 d (collectively “processing stations 502”) and a coverslipperstation 509. The apparatus 500 can process wet microscope slidescarrying freshly cut tissue specimens. An access door 530 can be opened,and a user can load specimen-bearing slides and coverslips into atransport device 518. The transport device 518 can sequentially deliverthe microscope slides to the processing stations 502 to automaticallyprocess (e.g., via a process that is substantially free of humanintervention) slides. As used herein, the term “processing station”includes, without limitation, a baking station, a material removalstation (e.g., a de-waxing station, a de-paraffinizing station, or thelike), staining station, or the like. For example, the processingstations 502 a, 502 b, 502 c, 502 d can be a baking station, ade-paraffinizing station, a staining station, and a baking/heatingstation, respectively. The number, location, and types of processingstations can be selected to provide the desired processing capability.The transport device 518 can deliver coverslips to the coverslipperstation 509, which can include, without limitation, one or morecoverslippers (e.g., coverslipper 300 or 400 of FIGS. 5-8), and thecoverslipped slides can be removed using the access door 530.

A controller 510 can be communicatively coupled to and command thetransport device 518, one or more of the processing stations 502, andthe coverslipper station 509. The controller 510 can generally include,without limitation, one or more computers, central processing units,processing devices, microprocessors, digital signal processors (DSPs),application-specific integrated circuits (ASICs), readers, and the like.To store information (e.g., executable instructions), the controller 510can include, without limitation, one or more storage elements, such ascomputer readable media, volatile memory, non-volatile memory, read-onlymemory (ROM), random access memory (RAM), or the like. The controller510 can include one or more processors that are programmed with a seriesof computer-executable instructions that are stored on a non-transitory,computer readable media. The stored computer-executable instructions caninclude detection programs, calibration programs, tissue preparationprograms, or other executable programs. Detection programs can beexecuted to detect coverslips using coverslip detectors of thecoverslipper station 509. The detection program can include, forexample, data for coverslips (e.g., optical characteristics) and cancompare the stored data to the signal from the coverslip detector. Basedon the comparison, the controller 510 can determine the number ofcoverslips. Optimization programs can be executed to optimizeperformance (e.g., increase productivity, enhance processingconsistency, or the like). The processing may be optimized bydetermining, for example, an optimum schedule to (1) increase processingspeeds, (2) reduce the coverslipping time, and/or (3) increasethroughput (e.g., increase the number of slides processed in a certainlength of time). The tissue preparation programs can be executed toperform tissue preparation protocols.

The transport device 518 can include, without limitation, one or moreelevators, slide handlers, slide trays, slide holders, or the like.Slide handlers can include, but are not limited to, slide manipulators,X-Y-Z transport systems, robotic systems, or other automated systemscapable of receiving and transporting slides and/or coverslips. Arobotic system can include, without limitation, one or more pick andplace robots, robotic arms, or the like.

FIG. 14 is a cross-sectional view of the apparatus 500 along line 14-14of FIG. 13. The transport device 518 can include a transporter 524, anelevator system 531, and a movable platform 534. The elevator system 531moves the transporter 524 up and down along a rail 540. A slide handler520, illustrated as a robotic slide handler, can transport slidesbetween the stations 502 and coverslipper station 509. The illustratedtransport device 518 is positioned to load the slides into theprocessing station 502 a.

Specimen-carrying microscope slides can be loaded onto a slide tray,which is placed on the platform 534. The slide handler 520 can load thespecimen-carrying microscope slides into the processing station 502 a.The processing station 502 a can dry the specimen-carrying microscopeslides. After the specimen-carrying microscope slides are dried asufficient amount, the slide transporter 524 can transport the slidesback to the tray. The transporter 542 can be vertically lowered andpositioned adjacent to the processing station 502 b forde-paraffinizing.

The de-paraffinizing station 502 b is capable of removing at least aportion of the embedding material of the specimen. The de-paraffinizingstation 502 b can be a bath-type, de-paraffinizing station or aspray-type, de-paraffinizing station. The illustrated de-paraffinizingstation 502 b includes a modular compartment 514 and includes one ormore wash dispense nozzles 516 directed downwardly. De-paraffinizingsubstances are delivered onto the specimens using the nozzles 516. Afterremoving the embedding material (e.g., paraffin), the slides can berinsed with substances, such as de-ionized water, to remove thede-paraffinizing substance and the extra paraffin leaving the baretissue sample adhered to the microscope slide. The de-paraffinizingsubstances can be fluids, for example, aqueous-based fluids that promoteseparation of paraffin and tissue specimens, such as those disclosed inU.S. Pat. No. 6,855,559, issued Feb. 15, 2005 and U.S. Pat. No.6,544,798, issued Apr. 8, 2003, including de-ionized water, citratebuffer (pH 6.0-8.0), tris-HCl buffer (pH 6-10), phosphate buffer (pH6.0-8.0), acidic buffers or solutions (pH 1-6.9), basic buffers orsolutions (pH 7.1-14), or the like. The substance may also contain oneor more ionic or non-ionic surfactants. The de-paraffinizing substancescan be heated. For example, the substances (e.g., fluids) may be heatedto a temperature greater than the melting point of the embeddingmaterial, e.g., between 60-70 degrees Celsius. U.S. Pat. No. 7,303,725,issued Dec. 4, 2007, discloses various components (e.g., probes,filters, sprayers, etc.) for use with de-paraffinizing substances. Insome embodiments, the station 502 b also includes one or more heatingelements for baking the embedding material. The slides can be heated tosoften the embedding material to facilitate material removal.

After the station 502 b has processed the specimen-carrying slides, thetransporter 524 can deliver the specimen-carrying slides to the station502 c for staining. A desired stain is applied by the staining station502 c to the tissue samples. The stain can be a biological or chemicalsubstance which, when applied to targeted molecules in tissue, rendersthe tissue detectable under an instrument. Stains include, withoutlimitation, detectable nucleic acid probes, antibodies, hematoxylin,eosin, and dyes (e.g., iodine, methylene blue, Wright's stain, etc.).For example, immunohistochemical and in situ hybridization stainingprocesses can be performed on the specimens.

After the specimens are stained, the specimen-bearing slides aretransported to the station 502 d capable of draining excess liquids(e.g., solvents) from the slides. After draining, the specimen-bearingslides are transported to the coverslipping station 509, which can besimilar or identical to the coverslipper 300 of FIGS. 5-7 or thecoverslipper 400 of FIG. 8. After the coverslipping station 509coverslips the slides, the coverslipped slides can be subsequentlyremoved from the apparatus 500.

The embodiments disclosed herein can also have other features forinhibiting or preventing light from returning back to the detectors. Insome embodiments, a reflective surface can be positioned behind thesurface of the coverslip opposite the optical sensor. The reflectivesurface can reflect light that travels through the coverslip(s) awayfrom the optical sensor. For example, the anti-reflective element 160 ofFIG. 1 can be a mirror or a reflective surface oriented to reflect lightaway from the detector 178 (FIG. 3). Other types of components can alsobe used to block or otherwise prevent light from returning back to theoptical sensor.

The detectors disclosed herein can be used to analyze different types ofitems. Such items can include, without limitation, semi-transparentsubstrates, transparent substrates, or other items capable of reflectinglight. For example, the detector 100 can detect substrates in the formof transparent sheets (e.g., screens for computers, screens for tablets,screens for smartphones, screens for touch screen devices, screens fortelevisions, etc.), watch glasses or crystals, or the like. In someembodiments, the detectors discloses herein can be incorporated tomanufacturing or production lines that assemble electronic devices(e.g., computers, tablets, smartphones, etc.), watches, or other deviceswith substrates.

From the foregoing, it will be appreciated that specific embodiments ofthe invention have been described herein for purposes of illustration,but well-known structures and functions have not been shown or describedin detail to avoid unnecessarily obscuring the description of at leastsome embodiments of the invention. Where the context permits, singularor plural terms may also include the plural or singular term,respectively. Unless the word “or” is associated with an express clauseindicating that the word should be limited to mean only a single itemexclusive from the other items in reference to a list of two or moreitems, then the use of “or” in such a list shall be interpreted asincluding (a) any single item in the list, (b) all of the items in thelist, or (c) any combination of the items in the list. The singularforms “a,” “an,” and “the” include plural referents unless the contextclearly indicates otherwise. Thus, for example, reference to “a sensor”refers to one or more sensors, such as two or more sensors, three ormore sensors, or four or more sensors.

In general, in the following claims, the terms used should not beconstrued to limit the claims to the specific embodiments disclosed inthe specification and the claims, but should be construed to include allpossible embodiments along with the full scope of equivalents to whichsuch claims are entitled. Accordingly, the claims are not limited by thedisclosure.

What is claimed is:
 1. A coverslip detector for detecting microscopeslide coverslips, the coverslip detector comprising: an opticallyanti-reflective element; and an optical sensor including a light sourcethat outputs light towards the optically anti-reflective element, and alight detector positioned to detect light from the light source that isreflected by one or more coverslips positioned within a coverslipdetection zone between the optical sensor and the opticallyanti-reflective element.
 2. The coverslip detector of claim 1, furthercomprising a coverslip holder mechanism movable from a loading positionfor obtaining at least one coverslip to a detection position for holdingthe at least one coverslip along an optical path from the light sourceto the optically anti-reflective element.
 3. The coverslip detector ofclaim 2, wherein the coverslip detector is configured to determine anumber of coverslips, if any, within the coverslip detection zone basedon the light from the light source that is reflected by the one or morecoverslips positioned within the coverslip detection zone, and theoptically anti-reflective element is configured to reduce or eliminateoptical noise with the light from the light source that is reflected bythe one or more coverslips positioned within the coverslip detectionzone.
 4. The coverslip detector of claim 2, wherein the optical sensorincludes a photoelectric proximity sensor.
 5. The coverslip detector ofclaim 1, further comprising a coverslip holder configured to hold atleast one coverslip along an optical path from the light source to theoptically anti-reflective element, the coverslip holder having a surfacefacing towards the light source, and wherein the opticallyanti-reflective element is positioned at the surface.
 6. The coverslipdetector of claim 5, wherein the optically anti-reflective elementincludes a black surface, a black coating, and/or a black film.
 7. Thecoverslip detector of claim 1, wherein the optically anti-reflectiveelement absorbs incident light from the light source such that thecoverslip detector is capable of determining a presence of a coverslipor number of coverslips at the coverslip detection zone.
 8. Thecoverslip detector of claim 1, wherein the optically anti-reflectiveelement prevents reflection of at least a portion of incident light fromthe optical sensor to enable the light detector to detect a number ofcoverslips in a stack of coverslips within the coverslip detection zone.9. The coverslip detector of claim 8, wherein the coverslip detector isconfigured to determine a presence or number of coverslips within thecoverslip detection zone based on the light detector detecting lightreflected by each of the coverslips in the stack of coverslips.
 10. Thecoverslip detector of claim 1, wherein the optically anti-reflectiveelement absorbs most of the light from the light source that strikes theoptically anti-reflective element.
 11. The coverslip detector of claim1, wherein the light detector detects light that is reflected by the oneor more coverslips at one or more wavelengths, and the opticallyanti-reflective element has a reflectivity equal to or less than about0.5 for the light at the one or more wavelengths.
 12. The coverslipdetector of claim 11, wherein the optically anti-reflective element hasa reflectivity of about 0.1 or less for the light at the one or morewavelengths.
 13. The coverslip detector of claim 1, wherein theoptically anti-reflective element includes a light-absorbing,low-remission surface that is less optically reflective than glass. 14.The coverslip detector of claim 1, wherein the optical sensor isconfigured to detect the light reflected by one or more coverslipspositioned within the coverslip detection zone while light from thelight source, which is transmitted through the one or more coverslips,strikes the optically anti-reflective element.
 15. The coverslipdetector of claim 1, further comprising a coverslip transport apparatusconfigured to carry at least one coverslip into and out of the coverslipdetection zone.
 16. The coverslip detector of claim 15, wherein thecoverslip transport apparatus includes a holder mechanism movable from aloading position for obtaining a coverslip to a detection position forholding the coverslip along an optical path extending from the lightsource to the optically anti-reflective element.
 17. The coverslipdetector of claim 16, wherein the optical sensor is spaced apart fromthe holder mechanism when the holder mechanism is at the detectionposition such that the holder mechanism is capable of holding two ormore coverslips spaced apart from the optical sensor.
 18. The coverslipdetector of claim 16, wherein the optically anti-reflective element is alow-remission surface of the holder mechanism.
 19. The coverslipdetector of claim 1, further comprising a controller in communicationwith the optical sensor, wherein the controller determines a presence ofone or more coverslips based, at least in part, on the light detected bythe optical sensor.
 20. The coverslip detector of claim 1, furthercomprising a controller in communication with the optical sensor andprogrammed to determine a number of the coverslips in the coverslipdetection zone based, at least in part, on the detected light.
 21. Anautomated slide processing apparatus, comprising: at least oneprocessing station configured to process a specimen on a microscopeslide; a coverslipper that receives microscope slides processed by theprocessing station, the coverslipper including an opticallyanti-reflective element; and an optical sensor including a light sourceand a light detector, wherein the light source is positioned to deliverlight along a path towards the optically anti-reflective element,wherein the light detector is positioned to detect light from the lightsource that is reflected by one or more coverslips positioned along thepath, and a transport mechanism configured to move microscope slidesbetween the processing station and the coverslipper.
 22. The automatedslide processing apparatus of claim 21, wherein the at least oneprocessing station includes a drying station, a de-paraffinizingstation, a staining station, or combination thereof.
 23. The automatedslide processing apparatus of claim 21, further comprising a controllercommunicatively coupled to the optical sensor and configured todetermine a number of coverslips carried by a holder mechanism of thecoverslipper.
 24. The automated slide processing apparatus of claim 23,wherein the controller has stored instructions specifying operationscomprising: if the holder mechanism of the coverslipper carries only onecoverslip, commanding the holder mechanism to place the coverslip on aslide; and if the holder mechanism of the coverslipper carries aplurality of coverslips, commanding the holder mechanism to deliver theplurality of coverslips to a coverslip collection station.
 25. A methodof detecting coverslips for microscope slides, comprising: deliveringlight towards at least one coverslip such that a portion of the light isreflected by the coverslip and a portion of the light travels throughthe at least one coverslip and strikes an optically anti-reflectiveelement; and detecting the light reflected by the at least one coverslipto determine a number of coverslips that reflected the light.
 26. Themethod of claim 25, further comprising determining the number ofcoverslips between the optically anti-reflective element and a lightsource, which outputted the light, by detecting light reflected by eachof the coverslips.
 27. The method of claim 25, further comprising atleast partially diffusing the portion of the light that travels throughthe at least one coverslip using the optically anti-reflective elementso as to reduce or eliminate optical noise to enhance detection of theportion of the light that is reflected by the at least one coverslip.28. The method of claim 25, further comprising: moving the at least onecoverslip into a detection zone of an optical sensor, wherein deliveringthe light includes outputting light from a light source of the opticalsensor while the at least one coverslip is positioned in the detectionzone such that the at least one coverslip reflects the light towards alight detector of the optical sensor.
 29. The method of claim 25,further comprising: holding the at least one coverslip against theoptically anti-reflective element while detecting the reflected light.30. The method of claim 25, wherein a ratio of a total amount of lightreflected by the optically anti-reflective element to a total amount oflight incident on the anti-reflective element is equal to or less thanabout 50%.
 31. The method of claim 25, further comprising: transportingthe at least one coverslip from a carrier containing a stack ofcoverslips to a detection position such that the at least one coverslipis positioned between the optically anti-reflective element and a lightsource of an optical sensor; and holding the at least one coverslip atthe detection position while the light source delivers light towards atleast one coverslip.
 32. The method of claim 25, further comprising: ifonly one coverslip is detected, placing the coverslip on a microscopeslide; and if a plurality coverslips are detected, transporting thecoverslips to a coverslip collection station.
 33. The method of claim25, further comprising: holding the at least one coverslip at adetection zone between a light source and the optically anti-reflectiveelement; if only one coverslip is detected at the detection zone,placing the coverslip on a microscope slide; and if a pluralitycoverslips are detected at the detection zone, transporting thecoverslips to a coverslip collection station.
 34. The method of claim25, further comprising absorbing light that travels through thecoverslip using the optically anti-reflective element such that acoverslip detector is capable of detecting light reflected by thecoverslip and determining a presence or number of coverslips based onthe detected light.
 35. A method of detecting substrates, comprising:carrying at least one substrate to a detection zone of an optical sensorusing a holder mechanism, wherein the detection zone is between a lightdetector of the optical sensor and an optically anti-reflective elementof the optical sensor; delivering light towards the substrate such thata portion of the light is reflected by the substrate and a portion ofthe light travels through the substrate and strikes the opticallyanti-reflective element; detecting the light reflected by the substrate;and determining a number of substrates at the detection zone based onthe detected light.
 36. The method of claim 35, further comprising:determining a delivery location based on the number of substrates; anddelivering the at least one substrate to the delivery location using theholder mechanism.
 37. The method of claim 35, wherein the substrate is amicroscope slide or a screen for an electronic device.